Microfracture with or without collagen scaffold insertion for adults with chondral or osteochondral defects of the knee: the SISMIC RCT and its challenges during and after the COVID-19 pandemic.

Background: Around 10,000 symptomatic knee articular cartilage injuries requiring repair occur annually in the United Kingdom, mostly in people under 35 years of age. Microfracture surgery aims to restore cartilage. Adding microstructural scaffolds made of collagen may further improve outcomes. Objectives: To evaluate the clinical and cost-effectiveness of microstructural scaffold in patients undergoing microfracture for a symptomatic chondral or osteochondral defect of the knee. Design: Multicentre, parallel two-group, superiority randomised controlled trial with blinding of participants, research staff and clinical care teams not involved in the surgery. Setting: National Health Service hospitals offering arthroscopic chondral surgery. Participants: Adults aged 18 years or older with symptomatic chondral or osteochondral defects of the knee on the medial or lateral femoral condyles, trochlea or patella and a chondral or osteochondral lesion measuring no more than 4 cm2. Exclusions were: unstable ligamentous injuries or meniscal tears that would not be treated; a knee with defects on the tibial chondral surface, < 50% native meniscal volume or requiring realignment surgery/osteotomy; and a lesion previously treated with microfracture. Interventions: Lesions were debrided, and microfracture was performed on the exposed subchondral bone. Intervention: microfracture of the chondral or osteochondral lesion with insertion of a bilayer collagen matrix microstructural scaffold, fixed with stiches or fibrin glue. Comparator: microfracture alone. Postoperative physiotherapy was standardised. Participants were randomised 1 : 1 between intervention and control. Main outcome measures: Primary outcome was the Knee Injury and Osteoarthritis Outcome Score at 24 months post randomisation. Secondary outcomes included International Knee Documentation Committee knee evaluation score; Tegner-Lysholm activity grading scale; EuroQol-5 Dimensions, five-level version; Work Productivity and Activity Impairment; complications and resource use measured at 3, 6, 12 and 24 months. Results: Twenty-two patients were screened across 8 sites, 20 of whom were eligible on screening. Of the 20 patients considered initially eligible, 2 patients were not interested and 1 opted for chondroplasty; the remaining 17 all consented to participate. Between November 2021 and October 2022, 10 participants were randomised, 5 to microfracture and 5 to microfracture with scaffold. Three patients failed the final in-surgery eligibility check (lesions had healed), one decided not to have surgery and three were still waiting when the study was closed. The median age was 38 years, and four participants were female. Most participants (seven) had damage to the lateral femoral condyle, and six had a medial and/or lateral meniscal tear. All participants received the allocated treatment and are included in the reported results. When a scaffold was used, the surgery took on average 10 minutes longer. There were three serious adverse events, knee pain and swelling in one participant, and a suspected anaphylactic reaction in another. Limitations: The SISMIC randomised controlled trial did not progress beyond the internal pilot phase due to insufficient recruitment. The target number of sites were opened, but recruitment was only 42% of the target 24 participants randomised. Insufficient data were collected to answer the research question. Conclusions: The SISMIC randomised controlled trial was severely impacted by the COVID-19 pandemic, the limited resources available at sites and the reduced elective orthopaedic surgical activity. Future work: To reflect contemporary practice, we recommend that a future trial evaluates three treatments: chondroplasty, chondroplasty with a microstructural scaffold and autologous chondrocyte implantation. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127849.